Is APOL4 p.Ala182Ser (c.544G>T) pathogenic?

APOL4 p.Ala182Ser (c.544G>T) is classified Likely benign in APOL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-01). AlphaMissense: likely benign (0.1619); Rare (popmax 0.576%, afr).

How common is APOL4 p.Ala182Ser (c.544G>T) in the general population?

APOL4 p.Ala182Ser (c.544G>T) is rare (popmax 0.576%, afr) (gnomAD).

What do computational predictors say about APOL4 p.Ala182Ser (c.544G>T)?

AlphaMissense predicts likely benign (score 0.1619) — an in-silico prediction, not a clinical call.

APOL4 p.Ala182Ser

c.544G>T · VCV4821418

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1619 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.576%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1619	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -5.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.68	GERP -1.8
Regional constraint	o/e 1.02	unconstrained · MANE · 11 kb · p 0.67 · regional, not allelic
Overall
CADD	0.849	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A185S vs ClinVar A182S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.576% African / African-American · 432/75,042 alleles

Filtering AF 0.531% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.513%

Overall 0.0295% 476/1,613,656 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.576%	174
Remaining individualsnot grpmax-eligible	0.04%	2,499
Admixed American	0.0217%	4,614
Middle Eastern	0.0165%	6,062
South Asian	0.0022%	45,509
European (non-Finnish)	0.000254%	393,235

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: APOL4
Protein: p.Ala182Ser
Coding: c.544G>T
MANE Select: NM_001386885
Type: single nucleotide variant
Location: chr22:36191578 (GRCh38)
Gene constraint: LOEUF 1.863 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.08

Full APOL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOL4 c.-3G>A Uncertain significance ★ same type
APOL4 p.Ala5Gly Uncertain significance ★ ⚠ same type
APOL4 p.Ala5Pro Uncertain significance ★ ⚠ same type
APOL4 p.Arg31His Uncertain significance ★ ⚠ same type
APOL4 p.Asp301Glu Uncertain significance ★ ⚠ same type
APOL4 p.Gly24Glu Uncertain significance ★ ⚠ same type
APOL4 p.His17Arg Uncertain significance ★ ⚠ same type
APOL4 p.Ile14Asn Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/apol4-p-ala182ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown